Liver transplantation is the most effective radical treatment for hepatocellular carcinoma (HCC), especially for patients with HCC complicated by cirrhosis. Since most patients are in an advanced stage of unresectable state when they are present, the preoperative downstaging treatment for liver transplantation in HCC is of great significance for increasing the opportunity for surgery, reducing the dropout rate from the liver transplant waiting list, and thereby lowering the postoperative recurrence rate. Currently, immune checkpoint inhibitor (ICI)-based combination immunotherapy and targeted therapy is the most effective treatment for preoperative downstaging in liver transplantation for HCC. However, the immunoenhancing effects of ICI may increase the risk of post-transplant rejection. Therefore, it is necessary to find a "critical point" that allows ICI to effectively inhibit tumor growth during preoperative downstaging treatment without causing severe rejection after transplantation. This article reviews the latest advances in preoperative ICI treatment protocols, efficacy assessment, indications, contraindications, drug discontinuation timing, and principles of prevention and treatment of rejection in liver transplantation for HCC.

OBJECTIVE To explore the effects of dexmedetomidine （DEX） increasing serpin peptidase inhibitor clade E member 1 （SERPINE1） protein on the malignant biological behavior of thyroid carcinoma （THCA） cells. METHODS THCA cells （KTC-1， TPC-1） were treated with 1， 10 and 100 nmol/L DEX， and their viabilities， clone formation rates， migration rates and invasion number were examined. Potential biological functions of DEX in THCA cells were analyzed through whole genome sequencing and gene ontology enrichment analysis. The core targets of DEX were mined through a protein-protein interaction network. The expression characteristics of DEX core targets and their relationship with patient prognosis were evaluated. The effects of DEX on mRNA and protein expressions of core targets and protein secretion in 2 types of THCA cells were detected， and the effects of this target on DEX-related effects were validated preliminarily by knocking down the core target. RESULTS Compared with the control group （0 nmol/L DEX）， DEX at 1， 10 and 100 nmol/L significantly increased the viabilities of 2 types of THCA cells （except for the KTC-1 cells in the 1 nmol/L DEX group at 24 h）， concentration-dependently elevated the rates of clone formation， migration rates （except for 2 types of THCA cells in 1 nmol/L DEX group）， and the number of invasion （P＜0.05）. A total of 287 differently expressed genes （75 up- tongxueyan180@163.com regulated and 212 down-regulated） were enriched in signaling pathways such as phosphatidylinositol 3-kinase/protein kinase B， Wnt， and senescence-associated secretory phenotypes in the 2 kinds of DEX-treated or non-treated THCA cells. SERPINE1 was a core target of DEX for THCA， and its mRNA and protein expression in THCA tissues/cells were significantly elevated and associated with poor prognosis of the patients （P＜0.05）. Compared with the control group， mRNA and protein expression of SERPINE1 was significantly up-regulated in 2 types of cells in the 1， 10 and 100 nmol/L DEX groups， while the secretion of this protein in conditioned medium was also significantly increased， all of which showed concentration-dependence （P＜0.05）. After knocking down SERPINE1， the promoting effects of DEX on the proliferation， colony formation， migration and invasion abilities of two types of THCA cells were significantly inhibited （P＜0.05）. CONCLUSIONS DEX can promote the proliferation， migration and invasion of THCA cell， and the above effects may be associated with the expression of increased secretory SERPINE1 protein.

OBJECTIVE To establish a pharmaceutical management model for infusion safety in hospitalized inpatients and ensure the safety of drug use. METHODS Our hospital established the standardized management process for infusion scheme， formulated rules for compatibility contraindications in drug combinations. In the form of embedded hospital official account, the infusion scheme and medication guidance WeChat developed by pharmacists are pushed to the mobile phone of inpatients, providing electronic medication guidance services for patients, and forming a pharmaceutical management model for infusion safety of inpatients. RESULTS Our hospital provided a total of 45 291 inpatients with pharmaceutical services including the formulation of individualized infusion scheme and WeChat push infusion scheme and medication guidance as of December 2023. After the implementation of the management model， the intervention rate of pharmacists on the compatibility contraindications in drug combination of long-term medical orders for inpatients increased from 18.25% before implementation to 90.58% （P＜0.01）， and the satisfaction rate of inpatients increased from 87.50% to 94.50% （P＜0.05）. CONCLUSIONS The pharmaceutical management model for infusion safety of hospitalized patients integrates pharmaceutical services throughout the entire process of intravenous medication treatment. Pharmacists can participate in the management of infusion usage while providing qualified finished infusion products, achieving closed-loop management of pharmaceutical services, improving the hospital’s pharmaceutical service capabilities and patient satisfaction, and providing guarantees for the safety and effectiveness of patient medication.

Objective To establish an acute rejection model of cervical heart transplantation in mice and evaluate the survival and dynamic rejection process post-transplantation. Methods Mice were randomly divided into sham operation group (n=10), syngeneic transplantation group (n=21), and allogeneic transplantation group (n=65). Sham operation, syngeneic cervical heart transplantation, and allogeneic cervical heart transplantation were performed respectively. The survival of recipient mice and grafts, histopathological changes of graft tissues, subpopulations of splenic lymphocytes, and expression of inflammatory factors in serum and grafts were observed. Results The survival rate and graft survival rate of the sham operation group and syngeneic transplantation group were 100% at 7 days after surgery. In the allogeneic transplantation group, 5 cases failed and died on the first day after surgery. The survival rate at 7 days after surgery was 86%, and all surviving mice had grafts that stopped beating at 7 days after surgery. The allogeneic transplantation group showed significant rejection at 7 days after surgery, accompanied by tissue damage and CD8⁺ T cell infiltration. The proportion of CD8⁺ T cells in the spleen continued to rise post-operation, while the proportion of CD4⁺ T cells showed a downward trend. The expression of interferon-γ in serum and grafts peaked at 5 days after surgery, while the expression of tumor necrosis factor-α showed no statistical significance. Conclusions Acute rejection following heart transplantation in mice intensifies between 5 to 7 days after surgery, which may be a critical time window for immunological intervention.

EGFR-mutant non-small cell lung cancer (NSCLC) is a common type of lung cancer, with EGFR tyrosine kinase inhibitors (EGFR-TKIs) being the standard first-line treatment. However, most patients with NSCLC eventually develop resistance to EGFR-TKIs. Studies on the mechanism underlying EGFR-TKI resistance have driven the development of personalized and precision medicine. Current strategies to address resistance include targeted therapy, immunotherapy, and novel drug treatments. Selecting the appropriate personalized treatment plan is crucial for improving the survival rate and quality of life of patients with EGFR-mutant NSCLC. Thus, this study provides a brief review of the current status and future perspectives in the treatment of EGFR-mutant NSCLC after progression on EGFR-TKI therapy.